Method of producing same



Patented July 24, 1934 i ALLYL' SUBSTITUTED ACETAMIDES AND METHOD OF PRODUCING SAME Karl Ziegler, Heidelberg, Germany, assignor to Schering-Kahlbaum A. G., Berlin, Germany,

No Drawing. Application April 2, 1932, Serial No. 602,873. In Germany May 13,.1931 L :7

9 Claims. (Cl. 2 60 -124) 7 My invention refers to chemical compounds having the characteristic-action of, soporirlcs and more especially to the amides of certain organic acids, which display this action.

5 Tertiary acetamides having a non-saturated alkyl group linked to the a-carbon atom, such as for instance diethyl allyl acetamide have already beenused as soporifics.

I have now discovered the surprising fact that 10 tertiary amides having two or three non-saturated alkyl groups linked to the u-carbon-atom, dis- ,play special properties as compared with the soporifics hitherto known. Comparative tests with (emulsions of the test substances in gum solutions, which were administered to rabbitsby means of a siphon sound, showed that the tertiary acetamidessubstituted with more than one nonsaturated alkylgroup were considerably more efficient than other soporifics including the diethyl allyl acetamide, the soporific dose being about milligrams per kilogram rabbit, while the other soporifics must be administered in greater doses. Thus for instance the lowest s0- porific dose of diethyl barbituric acid is 110 milligrams. Even with diethyl allyl acetamide the narcotic action only sets in with a dose of milligrams per kilogram rabbit.

I have further found that in the case of the barbituric acids only a small difference exists beno tween the smallest and the full narcotic dose, in contradistinction to the tertiary amides with more than one non-saturated alkyl group linked to the a-carbon atom displaying a great therapeutical width, i. e. a considerable difference between the minimum and full narcotic doses.

No such result could be expected, for the connections between constitution and narcotic action are not always such that the presence of a greater number of certain efficient groups also means greater efficiency. Thus for instance according to Frankels "Arzneimittel-Synthese (5th edition, p. 496) the substitution by a single phenyl group in acetamide is known to produce a narcotic action, while the substitution by two phenyl groups, as in diphenyl acetamide, shows no increase in the narcotic efiect.

The substitution by saponification is eifected amides on nitriles, such as acetonitrile or primary or secondary analogous derivatives thereof having the general formula RX, wherein X is halogen and R is a saturated or non-saturated alkylor aralkylor a non-aromatic isocyclic 60 group, which can in their turn be substituted by atoms or groups non-reacting or only slowly reacting with alkali metal amides, such as halogen atoms, alkoxy-, aryloxy-, arylmercapto or alkylated amino-groups. e From these starting products I have produced amongst others:

Triallyl acetamide, ethyl diallyl acetamide and n-propyl diallyl acetamide, being colourless crystals melting at 66, 65 and 53 C., respectively, 70 and dissolving in water only with difiiculty but being easily re-crystallizable from petrolether;

IIn practicing my invention I may for instance proceed as follows:

Example 1 '15 200 parts by weight triallyl acetonitrile are boiled 5 hours under the reflux condenser in a solution of 140 parts caustic potash in 1200 parts butanol. When the reaction has come to an end, the butanol is distilled off with steam. On 0001- ing down the residue solidifies in the form of crystals. After filtration by suction it is washed with water to remove the alkali, thereafter dried and recrystallized repeatedly from petrol. The triallyl acetamide thus obtained having the formula melts at 65 C. It is white-coloured and crystalline and behaves from a chemical point of view similarly to the triallyl acetamide.

Escample 3 300 parts diallyl-n-propyl acetonitrile are boiled 5 hours under the reflux condenser in a solution of 208 parts caustic potash in 1800 parts butanol. The reaction product is treated as described with reference to Example 1.

The diallyl-n-propyl acetamide thus obtained, which has the formula tuted by non-saturated radicles, having the formula c-ooNHz wherein R. is an ally-l radicle, R a saturated alkyl radicle or an allyl radicle, these products being colourless substances dissolving in water only with difficulty and having a powerful narcotic action.

2. As a new product, triallyl acetamide having the form of colourless crystals melting at 66 C. and dissolving in water only with difiiculty, the product having a powerful narcotic action.

3. As a new product, ethyl diallyl acetamide having the form of colourless crystals melting at C. and dissolving in water only with difficulty, the product having a powerful narcotic action.

4. As a new product, n-propyl diallyl acetamide having the form of colourless crystals melting at 53 C. and dissolving in water only with difiiculty, the product having a powerful narcotic action.

5. The method of producing tertiary acetamides substituted by allyl radicles and having a powerful narcotic action, comprising converting a tertiary acetonitrile having more than one allyl group linked to the u-carbon atom into the corresponding amide. v

' 6. The method of producing tertiary acetamides substituted by allyl radicles and having a powerful 'narcotic action, comprising alkylating acetoacetamide, comprising acting on diallyl-n-propyl acetonitrile with caustic alkali for saponification.

KARL ZIEGLER. 

